{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:26:30Z","timestamp":1780082790897,"version":"3.54.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T00:00:00Z","timestamp":1736553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background\/Objectives: Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding the association between serum levels of vitamin K2 analogs in different CAD types and examines their correlations with clinical risk parameters in CAD patients. Methods: This case\u2013control study enrolled CAD patients and healthy controls to assess and compare serum concentrations of two vitamin K2 analogs including menaquinone-4 (MK-4) and menaquinone-7 (MK-7) via ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS\/MS). CAD risk factors were evaluated and related to serum levels of vitamin K2 analogs. The CAD group was further subdivided into stable angina, STEMI, NSTEMI, and unstable angina groups to investigate potential differences in vitamin K2 analog levels. Results: Patients experiencing acute coronary syndrome exhibited notably reduced serum levels of MK-4 and MK-7 (1.61 \u00b1 0.66, and 1.64 \u00b1 0.59 ng\/mL, respectively) in comparison to the control group (2.29 \u00b1 0.54, and 2.16 \u00b1 0.46 ng\/mL, respectively), with MK-4 and MK-7 displaying stronger associations with CAD risk indicators. Notable variations in vitamin K2 analog levels were found between CAD patients and control groups (p &lt; 0.001). Unstable angina patients showed the lowest serum levels of MK-4 and MK-7. Conclusions: The present study demonstrated a higher prevalence rate of vitamin K2 deficiency among patients with CAD. The most pronounced decrease in MK-4 and MK-7 was observed in unstable angina patients. Moreover, these outcomes indicate the imperative requirement for an integrative approach that incorporates metabolic, lipid, and vitamin K2-related pathways in the risk stratification and management of CAD.<\/jats:p>","DOI":"10.3390\/diseases13010012","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T04:01:52Z","timestamp":1736740912000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence of Vitamin K2 Deficiency and Its Association with Coronary Artery Disease: A Case\u2013Control Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9624-6846","authenticated-orcid":false,"given":"Sameh A.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz A.","family":"Yar","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas M.","family":"Ghaith","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayan N.","family":"Alahmadi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal A.","family":"Almaleki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan S.","family":"Alahmadi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed H.","family":"Almaramhy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Alsaedi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man K.","family":"Alraddadi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein M.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Taibah University, Madinah 42353, Saudi Arabia"},{"name":"Department of Cardiology, College of Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.37616\/2212-5043.1336","article-title":"Cardiovascular Disease in Saudi Arabia: Facts and the Way Forward","volume":"35","author":"Tash","year":"2023","journal-title":"J. Saudi Hear. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.7326\/M14-1753","article-title":"Cardiovascular Mortality Associated with 5 Leading Risk Factors: National and State Preventable Fractions Estimated from Survey Data","volume":"163","author":"Patel","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00223-013-9712-z","article-title":"Vascular Calcification: An Update on Mechanisms and Challenges in Treatment","volume":"93","author":"Wu","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dube, P., DeRiso, A., Patel, M., Battepati, D., Khatib-Shahidi, B., Sharma, H., Gupta, R., Malhotra, D., Dworkin, L., and Haller, S. (2021). Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall. Biomedicines, 9.","DOI":"10.3390\/biomedicines9040404"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1111\/j.1523-1755.2004.00895.x","article-title":"Vascular Calcification: A Stiff Challenge for the Nephrologist: Does Preventing Bone Disease Cause Arterial Disease","volume":"66","author":"Goldsmith","year":"2004","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Perone, F., Bernardi, M., Redheuil, A., Mafrica, D., Conte, E., Spadafora, L., Ecarnot, F., Tokgozoglu, L., Santos-Gallego, C.G., and Kaiser, S.E. (2023). Role of Cardiovascular Imaging in Risk Assessment: Recent Advances, Gaps in Evidence, and Future Directions. J. Clin. Med., 12.","DOI":"10.3390\/jcm12175563"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s13668-017-0208-8","article-title":"The Role of Vitamin K Status in Cardiovascular Health: Evidence from Observational and Clinical Studies","volume":"6","author":"Beulens","year":"2017","journal-title":"Curr. Nutr. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e001715","DOI":"10.1136\/openhrt-2021-001715","article-title":"Vitamin K2-a Neglected Player in Cardiovascular Health: A Narrative Review","volume":"8","author":"Hariri","year":"2021","journal-title":"Open Hear."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1111\/j.1538-7836.2007.02758.x","article-title":"Post-Translational Modifications Regulate Matrix Gla Protein Function: Importance for Inhibition of Vascular Smooth Muscle Cell Calcification","volume":"5","author":"Schurgers","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1159\/000124863","article-title":"The Circulating Inactive Form of Matrix Gla Protein (UcMGP) as a Biomarker for Cardiovascular Calcification","volume":"45","author":"Cranenburg","year":"2008","journal-title":"J. Vasc. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/14017431.2019.1655166","article-title":"Association of Circulating Osteocalcin with Cardiovascular Disease and Intermediate Cardiovascular Phenotypes: Systematic Review and Meta-Analysis","volume":"53","author":"Seidu","year":"2019","journal-title":"Scand. Cardiovasc. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3945\/an.112.001834","article-title":"Vitamin K-Dependent Carboxylation of Osteocalcin: Friend or Foe?","volume":"3","author":"Gundberg","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2862","DOI":"10.1002\/dmrr.2862","article-title":"Carboxylated and Undercarboxylated Osteocalcin in Metabolic Complications of Human Obesity and Prediabetes","volume":"33","author":"Razny","year":"2017","journal-title":"Diabetes. Metab. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1021\/acs.langmuir.3c02948","article-title":"Osteocalcin: Promoter or Inhibitor of Hydroxyapatite Growth?","volume":"40","author":"Tavakol","year":"2024","journal-title":"Langmuir"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s40618-022-01744-3","article-title":"Osteocalcin-Expressing Endothelial Progenitor Cells and Serum Osteocalcin Forms Are Independent Biomarkers of Coronary Atherosclerotic Disease Severity in Male and Female Patients","volume":"45","author":"Shahrour","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shioi, A., Morioka, T., Shoji, T., and Emoto, M. (2020). The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification. Nutrients, 12.","DOI":"10.3390\/nu12020583"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1002\/fsn3.3213","article-title":"The Biological Responses of Vitamin K2: A Comprehensive Review","volume":"11","author":"Yan","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.2147\/JIR.S445806","article-title":"Vitamin K: Infection, Inflammation, and Auto-Immunity","volume":"17","author":"Xie","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/ajcn\/nqaa082","article-title":"Vitamin K Status, Cardiovascular Disease, and All-Cause Mortality: A Participant-Level Meta-Analysis of 3 US Cohorts","volume":"111","author":"Shea","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Chhonker, Y.S., Bala, V., Hagg, A., Snetselaar, L.G., Wahls, T.L., and Murry, D.J. (2020). Reversed Phase UPLC\/APCI-MS Determination of Vitamin K1 and Menaquinone-4 in Human Plasma: Application to a Clinical Study. J. Pharm. Biomed. Anal., 183.","DOI":"10.1016\/j.jpba.2020.113147"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"971453","DOI":"10.1155\/2015\/971453","article-title":"Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders","volume":"2015","author":"Upadhyay","year":"2015","journal-title":"J. Lipids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2147\/VHRM.S379874","article-title":"A Heart-Healthy Diet for Cardiovascular Disease Prevention: Where Are We Now?","volume":"19","author":"Diab","year":"2023","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1161\/CIRCULATIONAHA.122.059678","article-title":"High-Sensitivity Cardiac Troponin and the 2021 AHA\/ACC\/ASE\/CHEST\/SAEM\/SCCT\/SCMR Guidelines for the Evaluation and Diagnosis of Acute Chest Pain","volume":"146","author":"Sandoval","year":"2022","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1002\/ehf2.14063","article-title":"Association of Ejection Fraction with Mortality and Cardiovascular Events in Patients with Coronary Artery Disease","volume":"9","author":"Liu","year":"2022","journal-title":"ESC Hear. Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.2337\/db18-0543","article-title":"Circulating Phylloquinone Concentrations and Risk of Type 2 Diabetes: A Mendelian Randomization Study","volume":"68","author":"Zwakenberg","year":"2018","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.jacc.2007.07.051","article-title":"Platelet Function Monitoring in Patients with Coronary Artery Disease","volume":"50","author":"Gurbel","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jankowski, P., Kozie\u0142, P., Setny, M., Paniczko, M., Haberka, M., Banach, M., De Bacquer, D., De Backer, G., Kotseva, K., and Wood, D. (2021). Dyslipidemia Management in Patients with Coronary Artery Disease. Data from the POLASPIRE Survey. J. Clin. Med., 10.","DOI":"10.3390\/jcm10163711"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e435","DOI":"10.1161\/CIR.0000000000000207","article-title":"Treatment of Hypertension in Patients with Coronary Artery Disease","volume":"131","author":"Rosendorff","year":"2015","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1007\/s00394-020-02352-8","article-title":"Combined Low Vitamin D and K Status Amplifies Mortality Risk: A Prospective Study","volume":"60","author":"Beulens","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2147\/VHRM.S312376","article-title":"Vitamin D and Its Metabolites Deficiency in Acute Coronary Syndrome Patients Undergoing Coronary Angiography: A Case\u2013Control Study","volume":"17","author":"Ismail","year":"2021","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3945\/an.111.001644","article-title":"Vitamin K Status and Vascular Calcification: Evidence from Observational and Clinical Studies","volume":"3","author":"Shea","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mandatori, D., Pelusi, L., Schiavone, V., Pipino, C., Di Pietro, N., and Pandolfi, A. (2021). The Dual Role of Vitamin K2 in \u201cBone-Vascular Crosstalk\u201d: Opposite Effects on Bone Loss and Vascular Calcification. Nutrients, 13.","DOI":"10.3390\/nu13041222"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jadhav, N., Ajgaonkar, S., Saha, P., Gurav, P., Pandey, A., Basudkar, V., Gada, Y., Panda, S., Jadhav, S., and Mehta, D. (2022). Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.896920"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, T., Wang, Y., and Tu, W. (2023). Vitamin K Supplementation and Vascular Calcification: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1115069"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vlasschaert, C., Goss, C.J., Pilkey, N.G., McKeown, S., and Holden, R.M. (2020). Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials. Nutrients, 12.","DOI":"10.3390\/nu12102909"}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/1\/12\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:27:04Z","timestamp":1759919224000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/1\/12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,11]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["diseases13010012"],"URL":"https:\/\/doi.org\/10.3390\/diseases13010012","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,11]]}}}